The broad aim of this project is to gain insight into the mechanisms controlling growth and differentiation of muscle tissue. We will emphasize analysis of transcriptional and translational control of myofibrillar protein synthesis in both adult cardiac muscle and in differentiating embryonic skeletal and cardiac muscle. Changes in transcription of mRNAs for myosin heavy chains will be evaluated by the hybridization of cDNA probes transcribed from isolated and purified mRNAs. Comparison of rates of mRNA accumulation with rate of synthesis of individual proteins would indicate the relative role of transcriptional and translational control in the growth process. We will also evaluate the possibility that cardiac muscle contains more than one type of myosin heavy chain. We propose to use the recently introduced procedure of monoclonal antibodies to isolate and characterize putative myosin heavy chain variants. The second major aspect of this proposal is to examine transcription in developing skeletal and cardiac muscle. The chick embryo system will be used at least initially because of the advanced state of our knowledge of this system. We propose to isolate mRNAs for fast and slow myosin heavy chains. cDNAs transcribed from these mRNAs will be used to monitor transcription of individual mRNAs during embryonic development, in tissue culture and in defined physiological experiments. For the final purification of the individual mRNAs cloning of the cDNA plasmid recombinant molecules will be carried out. This procedure would serve to identify unequivocally probes for specific transcripts and for the structural genes. The probe could then be used to isolate structural genes for these proteins. This would allow examination of intragenic architecture, and analysis of neighboring sequences which may be involved in the regulation of synthesis of mRNAs for myofibrillar proteins during differentiation.